Produção Nacional
Revisado por pares
Identification of constrained sequence elements across 239 primate genomes
2023; Nature Portfolio; Volume: 625; Issue: 7996 Linguagem: Inglês
10.1038/s41586-023-06798-8
ISSN1476-4687
AutoresLukas F. K. Kuderna, Jacob C. Ulirsch, Sabrina Mohd Rashid, Mohamed Ameen, Laksshman Sundaram, Glenn Hickey, Anthony J. Cox, Hong Gao, Arvind Kumar, François Aguet, Matthew J. Christmas, Hiram Clawson, Maximilian Haeussler, Mareike C. Janiak, Martin Kuhlwilm, Joseph D. Orkin, Thomas Bataillon, Shivakumara Manu, Alejandro Valenzuela, Juraj Bergman, Marjolaine Rouselle, Felipe Ennes Silva, Lídia Águeda, Julie Blanc, Marta Gut, Dorien de Vries, Ian Goodhead, R. Alan Harris, Muthuswamy Raveendran, Axel Jensen, Idriss S. Chuma, Julie E. Horvath, Christina Hvilsom, David Juan, Peter Frandsen, Joshua G. Schraiber, Fabiano Rodrigues de Melo, Fabrício Bertuol, Hazel Byrne, Iracilda Sampaio, Izeni Pires Farias, João Valsecchi, Malu Messias, Maria Nazareth Ferreira da Silva, Mihir Trivedi, Rogério Vieira Rossi, Tomas Hrbek, Nicole Andriaholinirina, C. Rabarivola, Alphonse Zaramody, Clifford J. Jolly, Jane E. Phillips‐Conroy, Gregory K. Wilkerson, Christian R. Abee, Joe H. Simmons, Eduardo Fernández‐Duque, Sree Kanthaswamy, Fekadu Shiferaw, Dong‐Dong Wu, Long Zhou, Yong Shao, Guojie Zhang, Julius D. Keyyu, Sascha Knauf, Minh Đức Lê, Esther Lizano, Stefan Merker, Arcadi Navarro, Tilo Nadler, Chiea Chuen Khor, Jessica Lee, Patrick Tan, Weng Khong Lim, Andrew C. Kitchener, Dietmar Zinner, Marta Gut, Amanda Melin, Katerina Guschanski, Mikkel Heide Schierup, Robin M. D. Beck, Ioannis Karakikes, Ke Wang, Govindhaswamy Umapathy, Christian Roos, Jean P. Boubli, Adam Siepel, Anshul Kundaje, Benedict Paten, Kerstin Lindblad‐Toh, Jeffrey Rogers, Tomás Marquès‐Bonet, Kyle Kai‐How Farh,
Tópico(s)RNA Research and Splicing
ResumoAbstract Noncoding DNA is central to our understanding of human gene regulation and complex diseases 1,2 , and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome 3–9 . Identifying the genomic elements that have become constrained specifically in primates has been hampered by the faster evolution of noncoding DNA compared to protein-coding DNA 10 , the relatively short timescales separating primate species 11 , and the previously limited availability of whole-genome sequences 12 . Here we construct a whole-genome alignment of 239 species, representing nearly half of all extant species in the primate order. Using this resource, we identified human regulatory elements that are under selective constraint across primates and other mammals at a 5% false discovery rate. We detected 111,318 DNase I hypersensitivity sites and 267,410 transcription factor binding sites that are constrained specifically in primates but not across other placental mammals and validate their cis -regulatory effects on gene expression. These regulatory elements are enriched for human genetic variants that affect gene expression and complex traits and diseases. Our results highlight the important role of recent evolution in regulatory sequence elements differentiating primates, including humans, from other placental mammals.
Referência(s)